Ultrafiltration as a Therapy Option for

Diuretic Resistance: Inpatient & Outpatient

Case StudiesBeth Davidson DNP, ACNP,

CCRNKristi Hayes MSN, FNP

St. Thomas HospitalNashville, TN

Objectives Review the epidemiology and

pathophysiology of diuretic-resistant, acute heart failure

Identify volume overload treatment options

Review/discuss case studies of diuretic-resistance and use of ultrafiltration for volume removal

Epidemiology of Heart Failure (HF)

Heart failure is a major public health problem resulting in substantial morbidity and mortality

Major cost-driver of HF is high incidence of hospitalizations

JCAHO has initiated quality care indicators for hospitalized HF patients

CMS reimbursement for readmission < 30 days = $ 0

Population Group Prevalence Incidence Mortality

Hospital Discharges Cost

Total population 5,000,000 550,000 57,218 1,093,000 $29.6

billion

Insult

Cardiac Dysfunction

LV Remodeling

HemodynamicDecompensation

Preload Afterload

↓ Cardiac Output Renal

Vasoconstriction/Fluid Retention

NeurohormonalActivation RAAS/SNS Catecholamine Endothelin

Fluid Overload Symptoms

MorbidityDeath

Decompensated

Heart Failure

ACC/AHA Guidelines:Management of Fluid

Status Patients should not be discharged

from the hospital until a stable and effective diuretic regimen is established, and ideally, not until euvolemia is achieved

Patients who are sent home before these goals are reached are at high risk of recurrence of fluid retention and early readmission because unresolved edema may itself attenuate the response to diuretics

DiureticsCurrent “Standard of Care”

Diuretics…

More diuretics...

Still more diuretics…

7% 6%13%

26%

27%

16%

3% 2%

05

10

15

20

25

30

Enro

lled

Dis

char

ges

(%)

(<-20) (–20 to –15) (-15 to –10) (–10 to –5) (–5 to 0) (0 to 5) (5 to 10) (>10)

Change in Weight (lbs)

Nearly 50% of ADHF patients discharged with

weight gain or losing less than 5 lbs

Evidence of Incomplete Relief From Congestion

Change in Weight During Hospitalization

Outcomes with Standard Care

20%

50%

30Days

3Months

Hospital Readmissions

12%

50%

30Days

12Months

Mortality

33%

5Years

6Months

37%

Patients have persistently high event rates despite use of evidence-based therapies…

Outcomes with Standard Care

Loop Diuretic Inhibition of Macula

Densa

Increased Renin-Angiotensin

IncreasedAldosterone

Cardiac Remodeling and

Fibrosis

Left Ventricular Dysfunction

CARDIACFAILURE

Effect of Loop Diuretics on RAAS in Cardiac Failure

Favorable aspects of diuretic therapy Increases urine output; reduces total body

volume Adverse aspects of diuretic therapy

• Direct activation of renin-angiotensin-aldosterone system

• Enhanced myocardial aldosterone uptake• Loss of K, Mg, Ca, secondary myocyte Ca

loading• Indirect reduction of cardiac output• Increased total systemic vascular resistance• Reduced natriuresis and GFR• Associated with increased morbidity and

mortality

Current Options May Have Undesirable Clinical Impacts

Diuretics and ADHF No consensus dosing guidelines

No common definition of diuretic resistant

No long-term studies of diuretic therapy for the treatment of heart failure

No outcomes data regarding morbidity and mortality

14):39-42.

Diuretic Resistance Can be described as a clinical state

in which the diuretic response is diminished or lost before the therapeutic goal of relief from edema has been reached

Affects 20%–30% of patients with HF

Diuretic Resistance: Two Types

“Braking” phenomenon A decrease in response to a diuretic

after the first dose has been administered

Long-term tolerance Tubular hypertrophy to compensate for

salt loss

Diuretic Therapeutic Dilemma

Diminished renal function and concurrent sodium and water retention in ADHF presents a therapeutic dilemma with regard to sub-maximal diuretic therapy

Fluid removal by ultrafiltration may be recommended in this clinical setting

Method to safely achieve euvolemia Simplified form of ultrafiltration Inpatient or outpatient settings

ICU, CCU, MICU, telemetry, step-down, observation, ED, outpatient clinics

Peripheral or central venous access Flexible access sites and

catheters Diverse physician prescription Highly automated operation No clinically significant impact on

electrolyte balance, blood pressure, or heart rateor heart rate*

What is Aquapheresis?

Ultrafiltration can remove fluid from the blood at the same rate that fluid can be naturally recruited from the tissue

The transient removal of blood illicits compensatory mechanisms, termed plasma or intravascular refill (PR), aimed at minimizing this reduction

Fluid Removal by Ultrafiltration

VascularSpace

UF

VascularSpace

InterstitialSpace (edema)Na

Na

Na

Na

K

P

H2O

K

P

PR

The EUPHORIA Study Single center, prospective study, 20

patients Initial UF within 12 hours of

hospitalization and before any significant administration of IV diuretics and/or vasoactive drugs

Results Removed an average of 8.6 liters of

fluid 60% of patients were discharged in ≤ 3

days Average hospitalization was 3.7 days

The EUPHORIA Study Rehospitalization

In the three months preceding ultrafiltration:

10 hospitalizations in 9 patients

After ultrafiltration:1 readmission for ADHF within 30 days

The UNLOAD Study 200 patients (100 each arm)

randomized, multi-center study comparing ultrafiltration versus standard care for acutely decompensated patients

Superior salt & water removal/weight loss

At 48 hours, ultrafiltration demonstrated 38% greater weight loss 28% greater net fluid loss

At 90 days, reduced readmissions 50% reduction in re-hospitalization

episodes 63% reduction in total re-hospitalized

days 52% reduction in emergency

department or clinic visits

Ultrafiltration is reasonable for patients with refractory congestion not responding to medical therapy

ACC/AHA Guidelines: Class IIa, Level of Evidence B

I IIa IIb III

Aquapheresis is now ranked HIGHER in the Level of Evidence than:

- salt restriction- strict I/Os- higher doses of loop diuretics- addition of a second diuretic- continuous infusion of a loop diuretic- vasodilators – IV nitroglycerin, nesiritide- IV inotropes

All of these are Level of Evidence: C

Case Study 68 yo WM Diastolic heart

failure Ischemic heart

disease CAB 4/06

HTN Afibrillation/flutter Anemia Hospitalized every 6 months for

exacerbation

Case Study: Inpatient Therapy

Inpatient ultrafiltration – January 2010 Access issues – extended length

catheter (ELC) Creatinine 1.5 2.9 after 48 hrs of

treatment Creatinine 1.6 at discharge

Therapy/ACEI discontinued Diuresed with IV lasix continuous

infusion LOS = 5 days Net volume loss = 7 kgs

Case Study: Outpatient Therapy

1st treatment- 2/22/10 ELC catheter 1850 cc ultrafiltrate over 7 hrs Wt loss = 2 lbs Serum Cre = 1.8 pre and at termination

of therapy Hct 29 – sent home with hemoccult

cards Positive x 3- referred to PCP – no follow-up

Case Study: Outpatient Therapy

2nd treatment – 3/26/10 ELC catheter and 18 g peripheral IV

Access issues! 2130 ultrafiltrate over 6.5 hrs

Also treated with Lasix 240mg IV due to loss of time waiting for access

Serum Cre = 1.7 pre and post termination of therapy

Hct 26 - referred to Hematology

Saint Thomas Hospital:Inpatient Outcomes

54 UF treatments from 5/1/08 – 6/1/10

Average treatment time = 37 hours, 28 minutes

Average fluid removal = 6.15 liters/circuit

Minimal adverse events 9 episodes of worsening renal

insufficiency No significant electrolyte disturbances No significant hypotension 1 asymptomatic, small apical

pneumothorax 6 minor bleeding episodes – epistaxis,

line insertion site, generalized “oozing”

Saint Thomas Hospital:Inpatient Outcomes

Readmissions < 30 days 1 re-admitted with LOC changes 2 discharged to hospice

ultrafiltration for palliation 1 patient, 5 re-admissions

now on dialysis for volume control no readmits since dialysis except for recent

hip fracture 1 expired within 90 days of readmission 1 patient, 2 re-admissions

suspect non-compliance – eating Whopper at discharge!

Saint Thomas Hospital:Outpatient Outcomes

1st outpatient treatment – January 19, 2010 13 treatments – 7 pts

avg treatment time 5.79 hrs avg volume removal 1.49 L

1 repeated hospitalization now on peritoneal dialysis

1 deceased

1 ARF patient did not follow medication discharge instructions

Effective in keeping pts out of hospital > 30 days

Need more data Pt satisfaction and QOL are most important!

Advanced Heart Failure Clinic

Saint Thomas Hospital

Another satisfied customer…

Challenges andOpportunities for

Improvement Early identification of patients that

could benefit from outpatient therapy to decrease readmission within 30 days

Process improvement – timely, efficient IV access to allow faster initiation of therapy

Patient education – medications, line care, follow-up appointments, etc…

Anticoagulation – preserve integrity of circuit

Any questions?

Contact Information

Beth Davidson DNP, ACNP

bethdavidsondnp@comcast.net

Kristi Hayes MSN, FNPkhayes@stthomas.org